A Phase 2/3 Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD)

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This trial will assess the efficacy and safety of autologous CD34+ hematopoietic stem cells, transduced ex-vivo with Lenti-D lentiviral vector, for the treatment of cerebral adrenoleukodystrophy (CALD). A subject's blood stem cells will be collected and modified (transduced) using the Lenti-D lentiviral vector encoding human adrenoleukodystrophy protein. After modification (transduction) with the Lenti-D lentiviral vector, the cells will be transplanted back into the subject following myeloablative conditioning.

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Ages Eligible for Study:

up to 17 Years (Child)

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Informed consent is obtained from a competent custodial parent or guardian with legal capacity to execute a local IRB/Independent Ethics Committee (IEC) approved consent (informed assent will be sought from capable subjects, in accordance with the directive of the IRB/IEC and with local requirements).

Males aged 17 years and younger, at the time of parental/guardian consent and, where appropriate, subject assent.

Use of statins, Lorenzo's Oil, or dietary regimens used to lower VLCFA levels. Note: subjects must discontinue use of these medications at time of consent.

Receipt of an investigational study drug or procedure within 3 months before Screening that might confound study outcomes. Use of investigational study drugs is prohibited throughout the course of the study.

Any conditions that make it impossible to perform MRI studies (including allergies to anesthetics or contrast agents).

Hematological compromise as evidenced by:

Peripheral blood ANC count < 1500 cells/mm3,

Platelet count < 100,000 cells/mm3, or

Hemoglobin < 10 g/dL.

Uncorrected bleeding disorder.

Hepatic compromise as evidenced by:

Aspartate transaminase (AST) value > 2.5×ULN

Alanine transaminase (ALT) value > 2.5×ULN

Total bilirubin value > 3.0 mg/dL, except if there is a diagnosis of Gilbert's Syndrome and the subject is otherwise stable

Cardiac compromise as evidenced by left ventricular ejection fraction <40%

Immediate family member with a known or suspected familial cancer syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis).

Positive for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2); hepatitis B; hepatitis C; human T lymphotrophic virus 1 (HTLV-1). (Note that subjects who have been vaccinated against hepatitis B [hepatitis B surface antibody-positive] who are negative for other markers of prior hepatitis B infection [eg, negative for hepatitis B core antibody (Ab)] are eligible. Subjects with past exposure to HBV [HBcAb positive and/or HBeAb positive] are also eligible for the study provided they have a negative test for HBV DNA. Also note that subjects who are positive for anti-hepatitis C antibody are eligible as long as they have a negative hepatitis C viral load).

Any clinically significant cardiovascular or pulmonary disease, or other disease or condition that would be contraindicated for any of the other study procedures.

Absence of adequate contraception for fertile subjects. Male subjects and their female partners are required to use two different effective methods of contraception from Screening through at least 6 months after drug product infusion.